Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia.
Background Schizophrenia (SCZ) is a serious mental illness with complex pathology, including abnormalities in the glutamate system. Glutamate is rapidly removed from the synapse by excitatory amino acid transporters (EAATs). Changes in the expression and localization of the primary glutamate transpo...
| Publicado en: | Schizophrenia Bulletin Vol. 51; no. 2; pp. 531 - 543 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Mar2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=183817942&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 183817942 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 05867614 2CZ jtl: Schizophrenia Bulletin issn: 05867614 maglogo: N pubinfo: dt: Mar2025 vid: 51 iid: 2 pid: 622 pub: Oxford University Press / USA artinfo: ui: 183817942 183817942 183817942 10.1093/schbul/sbae092 183817942 ppf: 531 ppct: 12 formats: tig: atl: Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia. aug: au: O'Donovan, Sinead M Shan, Dan Wu, Xiaojun Choi, Jae Hyuk McCullumsmith, Robert E affil: Department of Neuroscience, University of Toledo, Toledo, OH, USA sug: subj: Schizophrenia Physiopathology Gene Expression Carrier Proteins Metabolism Neurons Metabolism Glutamic Acid Metabolism Glial Cells Metabolism Dorsolateral Prefrontal Cortex Metabolism Animal Studies Mice Path Analysis Comparative Studies Human Blotting, Western Polymerase Chain Reaction Regression Analysis of Covariance Descriptive Statistics Data Analysis Software Mann-Whitney U Test Nonparametric Statistics Antipsychotic Agents Therapeutic Use Funding Source ab: Background Schizophrenia (SCZ) is a serious mental illness with complex pathology, including abnormalities in the glutamate system. Glutamate is rapidly removed from the synapse by excitatory amino acid transporters (EAATs). Changes in the expression and localization of the primary glutamate transporter EAAT2 are found in the brain in central nervous system (CNS) disorders including SCZ. We hypothesize that neuronal expression and function of EAAT2 are increased in the frontal cortex in subjects diagnosed with SCZ. Study Design EAAT2 protein expression and glutamate transporter function were assayed in synaptosome preparations from the dorsolateral prefrontal cortex (DLPFC) of SCZ subjects and age- and sex-matched nonpsychiatrically ill controls. EAAT2 splice variant transcript expression was assayed in enriched populations of neurons and astrocytes from the DLPFC. Pathway analysis of publicly available transcriptomic datasets was carried out to identify biological changes associated with EAAT2 perturbation in different cell types. Results We found no significant changes in EAAT2 protein expression or glutamate uptake in the DLPFC in SCZ subjects compared with controls (n = 10/group). Transcript expression of EAAT2 and signaling molecules associated with EAAT2b trafficking (CaMKIIa and DLG1) were significantly altered in enriched populations of astrocytes and pyramidal neurons (P < .05) in SCZ (n = 16/group). These changes were not associated with antipsychotic medications. Pathway analysis also identified cell-type-specific enrichment of biological pathways associated with perturbation of astrocyte (immune pathways) and neuronal (metabolic pathways) EAAT2 expression. Conclusions Overall, these data support the growing body of evidence for the role of dysregulation of the glutamate system in the pathophysiology of SCZ. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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